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Brodhun, Florian
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Brodhun, Florian
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Brodhun, Florian
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Brodhun, F.
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2016Journal Article [["dc.bibliographiccitation.artnumber","e0167627"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Eng, Felipe"],["dc.contributor.author","Haroth, Sven"],["dc.contributor.author","Feussner, Kirstin"],["dc.contributor.author","Meldau, Dorothea"],["dc.contributor.author","Rekhter, Dmitrij"],["dc.contributor.author","Ischebeck, Till"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Feussner, Ivo"],["dc.date.accessioned","2018-11-07T10:05:11Z"],["dc.date.available","2018-11-07T10:05:11Z"],["dc.date.issued","2016"],["dc.description.abstract","Jasmonic acid is a plant hormone that can be produced by the fungus Lasiodiplodia theobromae via submerged fermentation. From a biotechnological perspective jasmonic acid is a valuable feedstock as its derivatives serve as important ingredients in different cosmetic products and in the future it may be used for pharmaceutical applications. The objective of this work was to improve the production of jasmonic acid by L. theobromae strain 2334. We observed that jasmonic acid formation is dependent on the culture volume. Moreover, cultures grown in medium containing potassium nitrate as nitrogen source produced higher amounts of jasmonic acid than analogous cultures supplemented with ammonium nitrate. When cultivated under optimal conditions for jasmonic acid production, L. theobromae secreted several secondary metabolites known from plants into the medium. Among those we found 3-oxo-2-(pent-2-enyI)-cyclopentane-1-butanoic acid (OPC-4) and hydroxy-jasmonic acid derivatives, respectively, suggesting that fungal jasmonate metabolism may involve similar reaction steps as that of plants. To characterize fungal growth and jasmonic acid-formation, we established a mathematical model describing both processes. This model may form the basis of industrial upscaling attempts. Importantly, it showed that jasmonic acid-formation is not associated to fungal growth. Therefore, this finding suggests that jasmonic acid, despite its enormous amount being produced upon fungal development, serves merely as secondary metabolite."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pone.0167627"],["dc.identifier.isi","000389482700213"],["dc.identifier.pmid","27907207"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14001"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38855"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Optimized Jasmonic Acid Production by Lasiodiplodia theobromae Reveals Formation of Valuable Plant Secondary Metabolites"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2012Journal Article [["dc.bibliographiccitation.firstpage","26"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","ChemistryOpen"],["dc.bibliographiccitation.lastpage","32"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Fehr, Friederike"],["dc.contributor.author","Nadler, Andre"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Feussner, Ivo"],["dc.contributor.author","Diederichsen, Ulf"],["dc.date.accessioned","2018-11-07T09:14:10Z"],["dc.date.available","2018-11-07T09:14:10Z"],["dc.date.issued","2012"],["dc.description.abstract","Total synthesis of proteins can be challenging despite assembling techniques, such as native chemical ligation (NCL) and expressed protein ligation (EPL). Especially, the combination of recombinant protein expression and chemically addressable solid-phase peptide synthesis (SPPS) is well suited for the redesign of native protein structures. Incorporation of analytical probes and artificial amino acids into full-length natural protein domains, such as the sequence-specific DNA binding zinc-finger motifs, are of interest combining selective DNA recognition and artificial function. The semi-synthesis of the natural 90 amino acid long sequence of the zinc-finger domain of Zif268 is described including various chemically modified constructs. Our approach offers the possibility to exchange any amino acid within the third zinc finger. The realized modifications of the natural sequence include point mutations, attachment of a fluorophore, and the exchange of amino acids at different positions in the zinc finger by artificial amino acids to create additional metal binding sites. The individual constructs were analyzed by circular dichroism (CD) spectroscopy with respect to the integrity of the zinc-finger fold and DNA binding."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) [IRTG 1422]"],["dc.identifier.doi","10.1002/open.201100002"],["dc.identifier.isi","000328606600005"],["dc.identifier.pmid","24551489"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8371"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27345"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","2191-1363"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","Semi-Synthesis and Analysis of Chemically Modified Zif268 Zinc-Finger Domains"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2016Journal Article [["dc.bibliographiccitation.artnumber","e0159875"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Bruckhoff, Viktoria"],["dc.contributor.author","Haroth, Sven"],["dc.contributor.author","Feussner, Kirstin"],["dc.contributor.author","Koenig, Stefanie"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Feussner, Ivo"],["dc.date.accessioned","2018-11-07T10:11:29Z"],["dc.date.available","2018-11-07T10:11:29Z"],["dc.date.issued","2016"],["dc.description.abstract","Over the past decades much research focused on the biosynthesis of the plant hormone jasmonyl-isoleucine (JA-Ile). While many details about its biosynthetic pathway as well about its physiological function are established nowadays, knowledge about its catabolic fate is still scarce. Only recently, the hormonal inactivation mechanisms became a stronger research focus. Two major pathways have been proposed to inactivate JA-Ile: i) The cleavage of the jasmonyl-residue from the isoleucine moiety, a reaction that is catalyzed by specific amidohydrolases, or ii), the sequential oxidation of the omega-end of the pentenyl side-chain. This reaction is catalyzed by specific members of the cytochrome P450 (CYP) subfamily CYP94: CYP94B1, CYP94B3 and CYP94C1. In the present study, we further investigated the oxidative fate of JA-Ile by expanding the analysis on Arabidopsis thaliana mutants, lacking only one (cyp94b1, cyp94b2, cyp94b3, cyp94c1), two (cyp94b1xcyp94b2, cyp94b1xcyp94b3, cyp94b2xcyp94b3), three (cyp94b1xcyp94b2xcyp94b3) or even four (cyp94b1xcyp94b2x-cyp94b3xcyp94c1) CYP94 functionalities. The results obtained in the present study show that CYP94B1, CYP94B2, CYP94B3 and CYP94C1 are responsible for catalyzing the sequential omega-oxidation of JA-Ile in a semi-redundant manner. While CYP94B-enzymes preferentially hydroxylate JA-Ile to 12-hydroxy-JA-Ile, CYP94C1 catalyzes primarily the subsequent oxidation, yielding 12-carboxy-JA-Ile. In addition, data obtained from investigating the triple and quadruple mutants let us hypothesize that a direct oxidation of unconjugated JA to 12-hydroxy-JA is possible in planta. Using a non-targeted metabolite fingerprinting analysis, we identified unconjugated 12-carboxy-JA as novel jasmonate derivative in floral tissues. Using the same approach, we could show that deletion of CYP94-genes might not only affect JA-homeostasis but also other signaling pathways. Deletion of CYP94B1, for example, led to accumulation of metabolites that may be characteristic for plant stress responses like systemic acquired resistance. Evaluation of the in vivo function of the different CYP94-enzymes on the JA-sensitivity demonstrated that particularly CYP94B-enzymes might play an essential role for JA-response, whereas CYP94C1 might only be of minor importance."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pone.0159875"],["dc.identifier.isi","000381515600059"],["dc.identifier.pmid","27459369"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13504"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40053"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Functional Characterization of CYP94-Genes and Identification of a Novel Jasmonate Catabolite in Flowers"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2013Journal Article [["dc.bibliographiccitation.artnumber","177"],["dc.bibliographiccitation.journal","BMC Plant Biology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Meyer, Danilo"],["dc.contributor.author","Herrfurth, Cornelia"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Feussner, Ivo"],["dc.date.accessioned","2018-11-07T09:17:38Z"],["dc.date.available","2018-11-07T09:17:38Z"],["dc.date.issued","2013"],["dc.description.abstract","Background: Oilseed germination is characterized by the degradation of storage lipids. It may proceed either via the direct action of a triacylglycerol lipase, or in certain plant species via a specific lipid body 13-lipoxygenase. For the involvement of a lipoxygenase previous results suggested that the hydroxy-or oxo-group that is being introduced into the fatty acid backbone by this lipoxygenase forms a barrier to continuous beta-oxidation. Results: This study shows however that a complete degradation of oxygenated fatty acids is possible by isolated cucumber and sunflower glyoxysomes. Interestingly, degradation is accompanied by the formation of saturated short chain acyl-CoAs with chain length between 4 and 12 carbon atoms lacking the hydroxy-or oxo-diene system of the oxygenated fatty acid substrate. The presence of these CoA esters suggests the involvement of a specific reduction of the diene system at a chain length of 12 carbon atoms including conversion of the hydroxy-group at C7. Conclusions: To our knowledge this metabolic pathway has not been described for the degradation of polyunsaturated fatty acids so far. It may represent a new principle to degrade oxygenated fatty acid derivatives formed by lipoxygenases or chemical oxidation initiated by reactive oxygen species."],["dc.description.sponsorship","Deutsche Forschungs Gemeinschaft [FE 446/4]"],["dc.identifier.doi","10.1186/1471-2229-13-177"],["dc.identifier.isi","000329069200001"],["dc.identifier.pmid","24207097"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10049"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28212"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2229"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Degradation of lipoxygenase-derived oxylipins by glyoxysomes from sunflower and cucumber cotyledons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2012Journal Article [["dc.bibliographiccitation.artnumber","228"],["dc.bibliographiccitation.journal","BMC Plant Biology"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Scholz, Julia"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Hornung, Ellen"],["dc.contributor.author","Herrfurth, Cornelia"],["dc.contributor.author","Stumpe, Michael"],["dc.contributor.author","Beike, Anna K."],["dc.contributor.author","Faltin, Bernd"],["dc.contributor.author","Frank, Wolfgang"],["dc.contributor.author","Reski, Ralf"],["dc.contributor.author","Feussner, Ivo"],["dc.date.accessioned","2018-11-07T09:03:11Z"],["dc.date.available","2018-11-07T09:03:11Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: The moss Physcomitrella patens contains C-18- as well as C-20-polyunsaturated fatty acids that can be metabolized by different enzymes to form oxylipins such as the cyclopentenone cis(+)-12-oxo phytodienoic acid. Mutants defective in the biosynthesis of cyclopentenones showed reduced fertility, aberrant sporophyte morphology and interrupted sporogenesis. The initial step in this biosynthetic route is the conversion of a fatty acid hydroperoxide to an allene oxide. This reaction is catalyzed by allene oxide synthase (AOS) belonging as hydroperoxide lyase (HPL) to the cytochrome P450 family Cyp74. In this study we characterized two AOS from P. patens, PpAOS1 and PpAOS2. Results: Our results show that PpAOS1 is highly active with both C-18 and C-20-hydroperoxy-fatty acid substrates, whereas PpAOS2 is fully active only with C-20-substrates, exhibiting trace activity (similar to 1000-fold lower k(cat)/K-M) with C-18 substrates. Analysis of products of PpAOS1 and PpHPL further demonstrated that both enzymes have an inherent side activity mirroring the close inter-connection of AOS and HPL catalysis. By employing site directed mutagenesis we provide evidence that single amino acid residues in the active site are also determining the catalytic activity of a 9-/13-AOS - a finding that previously has only been reported for substrate specific 13-AOS. However, PpHPL cannot be converted into an AOS by exchanging the same determinant. Localization studies using YFP-labeled AOS showed that PpAOS2 is localized in the plastid while PpAOS1 may be found in the cytosol. Analysis of the wound-induced cis(+)-12-oxo phytodienoic acid accumulation in PpAOS1 and PpAOS2 single knock-out mutants showed that disruption of PpAOS1, in contrast to PpAOS2, results in a significantly decreased cis(+)-12-oxo phytodienoic acid formation. However, the knock-out mutants of neither PpAOS1 nor PpAOS2 showed reduced fertility, aberrant sporophyte morphology or interrupted sporogenesis. Conclusions: Our study highlights five findings regarding the oxylipin metabolism in P. patens: (i) Both AOS isoforms are capable of metabolizing C-18- and C-20-derived substrates with different specificities suggesting that both enzymes might have different functions. (ii) Site directed mutagenesis demonstrated that the catalytic trajectories of 9-/13-PpAOS1 and PpHPL are closely inter-connected and PpAOS1 can be inter-converted by a single amino acid exchange into a HPL. (iii) In contrast to PpAOS1, PpAOS2 is localized in the plastid where oxylipin metabolism takes place. (iv) PpAOS1 is essential for wound-induced accumulation of cis(+)-12-oxo phytodienoic acid while PpAOS2 appears not to be involved in the process. (v) Knock-out mutants of neither AOS showed a deviating morphological phenotype suggesting that there are overlapping functions with other Cyp74 enzymes."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1186/1471-2229-12-228"],["dc.identifier.isi","000314283900001"],["dc.identifier.pmid","23194461"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8508"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24851"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2229"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Biosynthesis of allene oxides in Physcomitrella patens"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2013Journal Article [["dc.bibliographiccitation.artnumber","e64919"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PloS one"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Cristobal-Sarramian, Alvaro"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Newie, Julia"],["dc.contributor.author","Hamberg, Mats"],["dc.contributor.author","Feussner, Ivo"],["dc.date.accessioned","2019-07-09T11:40:02Z"],["dc.date.available","2019-07-09T11:40:02Z"],["dc.date.issued","2013"],["dc.description.abstract","Jasmonates constitute a family of lipid-derived signaling molecules that are abundant in higher plants. The biosynthetic pathway leading to plant jasmonates is initiated by 13-lipoxygenase-catalyzed oxygenation of α-linolenic acid into its 13-hydroperoxide derivative. A number of plant pathogenic fungi (e.g. Fusarium oxysporum) are also capable of producing jasmonates, however, by a yet unknown biosynthetic pathway. In a search for lipoxygenase in F. oxysporum, a reverse genetic approach was used and one of two from the genome predicted lipoxygenases (FoxLOX) was cloned. The enzyme was heterologously expressed in E. coli, purified via affinity chromatography, and its reaction mechanism characterized. FoxLOX was found to be a non-heme iron lipoxygenase, which oxidizes C18-polyunsaturated fatty acids to 13S-hydroperoxy derivatives by an antarafacial reaction mechanism where the bis-allylic hydrogen abstraction is the rate-limiting step. With α-linolenic acid as substrate FoxLOX was found to exhibit a multifunctional activity, because the hydroperoxy derivatives formed are further converted to dihydroxy-, keto-, and epoxy alcohol derivatives."],["dc.identifier.doi","10.1371/journal.pone.0064919"],["dc.identifier.fs","594675"],["dc.identifier.pmid","23741422"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10603"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58079"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.subject.mesh","Amino Acid Sequence"],["dc.subject.mesh","Fatty Acids"],["dc.subject.mesh","Fusarium"],["dc.subject.mesh","Hydrogen-Ion Concentration"],["dc.subject.mesh","Iron"],["dc.subject.mesh","Kinetics"],["dc.subject.mesh","Lipoxygenase"],["dc.subject.mesh","Mass Spectrometry"],["dc.subject.mesh","Molecular Sequence Data"],["dc.subject.mesh","Oxidation-Reduction"],["dc.subject.mesh","Phylogeny"],["dc.subject.mesh","Recombinant Fusion Proteins"],["dc.subject.mesh","Sequence Alignment"],["dc.title","An iron 13S-lipoxygenase with an α-linolenic acid specific hydroperoxidase activity from Fusarium oxysporum."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2011Journal Article [["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","95"],["dc.bibliographiccitation.journal","Frontiers in Plant Science"],["dc.bibliographiccitation.lastpage","24"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Ibrahim, Amina"],["dc.contributor.author","Schütz, Anna-Lena"],["dc.contributor.author","Galano, Jean-Marie"],["dc.contributor.author","Herrfurth, Cornelia"],["dc.contributor.author","Feussner, Kirstin"],["dc.contributor.author","Durand, Thierry"],["dc.contributor.author","Brodhun, Florian"],["dc.contributor.author","Feussner, Ivo"],["dc.date.accessioned","2019-07-09T11:53:15Z"],["dc.date.available","2019-07-09T11:53:15Z"],["dc.date.issued","2011"],["dc.description.abstract","Galactolipids constitute the major lipid class in plants. In recent years oxygenated derivatives of galactolipids have been detected. They are discussed as signal molecules during leaf damage, since they accumulate in wounded leaves in high levels. Using different analytical methods such as nuclear magnetic resonance, infra-red spectroscopy, and high performance liquid chromatography/mass spectrometry (HPLC/MS) earlier reports focused on the analysis of either oxidized or non-oxidized species and needed high levels of analytes. Here, we report on the analysis of the galactolipid subfraction of the Arabidopsis leaf lipidome by an improved HPLC/MS2-based method that is fast, robust, and comparatively simple in its performance. Due to a combination of phase partitioning, solid phase fractionation, liquid chromatography, and MS2 experiments this method has high detection sensitivity and requires only low amounts of plant material. With this method 167 galactolipid species were detected in leaves of Arabidopsis thaliana. Out of these 79 being newly described species. From all species the head group and acyl side chains were identified via MS2 experiments. Moreover, the structural identification was supported by HPLC/time-of-flight (TOF)-MS and gas chromatography (GC)/MS analysis. The quantification of different galactolipid species that accumulated 30 min after a mechanical wounding in A. thaliana leaves showed that the oxidized acyl side chains in galactolipids are divided into 65% cyclopentenones, 27% methyl-branched ketols, 3.8% hydroperoxides/straight-chain ketols, 2.0% hydroxides, and 2.6% phytoprostanes. In comparison to the free cyclopentenone derivatives, the esterified forms occur in a 149-fold excess supporting the hypothesis that galactolipids might function as storage compounds for cyclopentenones. Additional analysis of the ratio of non-oxidized to oxidized galactolipid species in leaves of wounded plants was performed resulting in a ratio of 2.0 in case of monogalactosyl diacylglycerol (MGD), 8.1 in digalactosyl diacylglycerol (DGD), and 0.6 in the acylated MGD. This indicates that galactolipid oxidation is a major and rapid metabolic process that occurs class specific."],["dc.identifier.doi","10.3389/fpls.2011.00095"],["dc.identifier.fs","587782"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7190"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60379"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Research Foundation"],["dc.relation.eissn","1664-462X"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.subject.ddc","570"],["dc.title","The alphabet of galactolipids in Arabidopsis thaliana"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI